Uncoupling of βIIPKC from its targeting protein RACK1 in response to ethanol in cultured cells and mouse brain

R. O.N. Dorit, Alicia J. Vagts, Douglas P. Dohrman, Rami Yaka, Zhan Jiang, Lina Yao, John Crabbe, Judith E. Grisel, Ivan Diamond

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Protein kinase C (PKC) is involved in many neuroadaptive responses to ethanol in the nervous system. PKC activation results in translocation of the enzyme from one intracellular site to another. Compartmentalization of PKC isozymes is regulated by targeting proteins such as receptors for activated C kinase (RACKs). It is possible, therefore, that ethanol-induced changes in the function and compartmentalization of PKC isozymes could be due to changes in PKC targeting proteins. Here we study the response of the targeting protein RACK1 and its corresponding kinase βIIPKC to ethanol, and propose a novel mechanism to explain how ethanol modulates signaling cascades. In cultured cells, ethanol induces movement of RACK1 to the nucleus without affecting the compartmentalization of βIIPKC. Ethanol also inhibits βIIPKC translocation in response to activation. These results suggest that ethanol inhibition of βIIPKC translocation is due to miscompartmentalization of the targeting protein RACK1. Similar events occurred in mouse brain. In vivo exposure to ethanol caused RACK1 to localize to nuclei in specific brain regions, but did not affect the compartmentalization of βIIPKC. Thus, some of the cellular and neuroadaptive responses to ethanol may be related to ethanol-induced movement of RACK1 to the nucleus, thereby preventing the translocation and corresponding function of βIIPKC.

Original languageEnglish (US)
Pages (from-to)2303-2314
Number of pages12
JournalFASEB Journal
Volume14
Issue number14
DOIs
StatePublished - Jan 1 2000

Keywords

  • Activated C hinase receptor
  • Ethanol
  • PKC
  • Signal transduction
  • Targeting protein
  • cAMP

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Dorit, R. O. N., Vagts, A. J., Dohrman, D. P., Yaka, R., Jiang, Z., Yao, L., Crabbe, J., Grisel, J. E., & Diamond, I. (2000). Uncoupling of βIIPKC from its targeting protein RACK1 in response to ethanol in cultured cells and mouse brain. FASEB Journal, 14(14), 2303-2314. https://doi.org/10.1096/fj.00-0143com